Vascular disorders, including vascular disorders associated with or contributing to complications in pregnancy often go undetected in subjects. Consequently, there is a need for improved methods for early prediction of vascular disorders in subjects at risk, and preferably before the disorder develops. While several risk factors predicting coronary heart disease or stroke have been identified, including hypertension, hyperlipidaemia, family history, diabetes and smoking, vascular events occur in up to 30% of subjects without these adverse risk factors. Despite optimal management of conditions manifested by such vascular disorders, vascular events continue to occur (in 10-20% of subjects per year) after presentation. Such facts underline the need for a better understanding of vascular disorders and improved means of detection and monitoring.
For example, a biomarker predictive of risk of a vascular disorder in a subject would improve treatment prospects by identifying those subjects before the development of pathological changes threatening organ function and/or adverse event occurrence during pregnancy, and hence would allow specific therapies to be individualised to at risk subjects.
C-type natriuretic peptide (CNP) belongs to a family of natriuretic peptides important in maintaining cardiovascular homeostasis. Distinct from the cardiac hormones ANP and BNP, CNP is expressed in a wide range of tissues including those of the central nervous system, reproductive system, skeleton and vascular endothelium. Regulation of endothelial CNP is still poorly understood but in vitro studies implicate a range of cytokines including TGF beta and other growth factors such as PDGFs and FGFs.
CNP acts locally and is rapidly degraded at the source, but products of CNP gene expression can be measured in plasma. Amino terminal propeptide of C-type natriuretic peptide (NTproCNP) in contrast is not rapidly degraded in the plasma and thus provides a new approach to measuring tissue CNP production in vivo (Prickett T C R et al. (2001) Biochemical and Biophysical Research Communications 286(3):513-517).
To the inventor's knowledge, there has only been one study where CNP and/or NTproCNP peptide levels have been examined in relation to endothelial function and vascular risk of development of arteriosclerosis. In that study of 117 older men selected in order to establish risk of vascular disease, lower concentrations of NTproCNP were associated with higher vascular risk scores and impaired endothelial function (Vlachopoulos C et al (2010) Atherosclerosis 211(2):649-55). These findings were consistent with the view that lower CNP within the vasculature (reflected by lower concentrations of the peptide in plasma) predispose subjects to arteriosclerosis. In contrast, the present inventors have found that in contrast to the only earlier study, increase in plasma NTproCNP is in fact associated with vascular risk.
In addition, there has been no previous examination of the role of CNP concentration, and in particular NTproCNP concentration in the pregnancy setting and in particular in pregnant subjects which develop a vascular-related adverse event during pregnancy.